Introduction
What if your cells could be fooled into thinking they're eating less, even when you're not? Recent research reveals a fascinating link between our cells' perception of nutrient levels and the aging process, offering potential new strategies to slow down aging.
The Cellular Messenger, mTOR
A team led by Alejo Efeyan, head of the Metabolism and Cell Signalling Group at the National Cancer Research Centre (CNIO), explored the relationship between nutrient intake and aging. They focused on mTOR, a protein complex crucial for cellular metabolism and energy utilization. By genetically manipulating mTOR’s activity, they tricked cells into believing they were receiving an excess of nutrients, despite a normal diet.
Accelerated Aging Through Inflammation
This cellular deception had dramatic consequences. As the animals matured, their cells malfunctioned, leading to accelerated aging. Their skin thinned, and vital organs like the pancreas, liver, and kidneys showed damage. Ana Ortega-Molina, head of the Metabolism in Cancer and Ageing Laboratory at the Severo Ochoa Molecular Biology Centre (CBM), explained, “The immune system cells come to repair them but are overwhelmed by the amount of damage. They accumulate and, instead of repairing, trigger inflammation that further increases problems in those organs.” This vicious cycle of damage and inflammation shortened the animals' lifespan by 20%, equivalent to about 16 years in humans.
Parallels with Natural Aging
The researchers found similarities between the genetically modified animals and naturally aging mice, such as reduced activity of lysosomes, the cellular "recycling centres." Efeyan noted, “When there is an excess of nutrients, it makes sense that the cell shuts down the recycling activity of lysosomes because this recycling operates especially when there are no nutrients.” This decrease in lysosomal activity also occurs in human aging, confirmed by blood samples from young people and septuagenarians.
Unlocking the Mysteries of Aging
Efeyan sees potential in this new animal model to uncover more about aging. “It’s a tool that many more people can use,” he said, envisioning studies on nutrient signalling’s effects on specific organs and neurodegenerative diseases. The research connects obesity, aging, and possible interventions for promoting longevity. It suggests that individuals with a higher body mass index (BMI), associated with excess nutrient intake, may experience accelerated aging due to mechanisms observed in the study.
Benefits of Calorie Restriction
The study also highlights the benefits of calorie restriction, known to extend lifespan in various organisms. Limiting nutrient intake could activate genes that interact with the mTOR pathway, potentially mitigating the adverse effects of excess nutrients on cellular function and aging.
Additional Advantages of Eating Less
Beyond promoting longevity, calorie restriction offers several health benefits. It improves metabolic health by enhancing insulin sensitivity, reducing the risk of type 2 diabetes, lowering blood pressure, and cholesterol levels, thus contributing to cardiovascular health. It also reduces oxidative stress by decreasing reactive oxygen species production, protecting against age-related conditions like Alzheimer’s and Parkinson’s diseases.
Calorie restriction boosts autophagy, a cellular process that removes and recycles damaged components, maintaining cellular health and preventing disease. It also strengthens the immune system by increasing infection-fighting cell production and improves mental health by enhancing mood and cognitive function, possibly through increased brain-derived neurotrophic factor (BDNF) levels, a protein that supports neuron growth and survival.
The Study’s Significance
This study illuminates the complex relationship between nutrient perception and aging. By manipulating the mTOR protein complex, researchers have shown how overeating signals can accelerate aging in animal models. This groundbreaking research opens new avenues for therapeutic interventions and understanding aging mechanisms in humans, showcasing the power of scientific inquiry to improve our health and well-being as we age.
References
- Efeyan, A., et al. Altering mTOR Activity to Understand Nutrient Signalling and Aging. National Cancer Research Centre (CNIO).
- Ortega-Molina, A., et al. Inflammation and Accelerated Aging. Severo Ochoa Molecular Biology Centre (CBM).
- Journal of Metabolism and Cell Signalling.
- International Journal of Environmental Research and Public Health.
- Research on Calorie Restriction and Longevity, Neurology Journal.